Abnormal Levels of Circulating Endothelial Progenitor Cells During Exacerbations of COPD Ernest Sala • Cristina Villena • Catalina Balaguer • Angel Rı ´os • Carlos Ferna ´ndez-Palomeque • Borja G. Cosı ´o • Javier Garcı ´a • Aina Noguera • Alvar Agustı ´ Received: 27 August 2009 / Accepted: 29 December 2009 / Published online: 14 January 2010 Ó Springer Science+Business Media, LLC 2010 Abstract Cardiovascular morbidity and mortality is increased in patients with chronic obstructive pulmonary disease (COPD). Reduced levels of circulating endothelial progenitor cells (EPCs) are associated with increased risk of death in patients with stable coronary artery disease (CAD). Likewise, during acute events of CAD, the number of cir- culating EPCs increases under the influence of vascular endothelial growth factor (VEGF) and systemic inflammation. Abnormal levels of circulating EPCs have been reported in patients with COPD. However, the response of EPCs to episodes of exacerbation of the disease (ECOPD) has not been investigated yet. We hypothesized that similar to what occurs during acute events of CAD, levels of circulating EPCs would increase during ECOPD. We compared levels of circulating EPCs (assessed by the % of CD34 ? KDR ? cells determined by flow cytometry) in patients hospitalized because of ECOPD (n = 35; 65 ± 9 years [mean ± SD]; FEV 1 = 46 ± 15% pre- dicted), patients with stable COPD (n = 44; 68 ± 8 years; FEV 1 = 49 ± 17% predicted), smokers with normal lung function (n = 10; 60 ± 9 years), and healthy never smok- ers (n = 10; 62 ± 4 years). To investigate potential mechanisms of EPC regulation, we assessed both VEGF and high-sensitivity C-reactive protein (hsC-RP) in plasma. Our results show that EPC levels were higher (p \ 0.05) in patients with ECOPD (1.46 ± 1.63%) than in those with stable disease (0.68 ± 0.83%), healthy smokers (0.65 ± 1.11%), and healthy never smokers (1.05 ± 1.36%). The percentage of circulating EPCs was positively related to VEGF plasma levels during ECOPD (r = 0.51, p = 0.003). In a subset of 12 patients who could be studied during both ECOPD and clinical stability, the EPCs levels increased during ECOPD. We conclude that EPC levels are increased during ECOPD, likely in relation to VEGF upregulation. Keywords Chronic bronchitis Á Emphysema Á Inflammation Á VEGF Á COPD exacerbation Introduction Endothelial progenitor cells (EPCs), capable of trans- forming into mature, functional endothelial cells, can be E. Sala (&) Á C. Balaguer Á B. G. Cosı ´o Servei de Pneumologia, Hospital Universitari Son Dureta, C/ Andrea Doria 55, 07014 Palma de Mallorca, Spain e-mail: ernest.sala@ssib.es C. Ferna ´ndez-Palomeque Servei de Cardiologı ´a, Hospital Universitari Son Dureta, Palma de Mallorca, Spain A. Noguera Servei de Ana `lisi Clı ´niques, Hospital Universitari Son Dureta, Palma de Mallorca, Spain J. Garcı ´a Emergency Department, Hospital Universitari Son Dureta, Palma de Mallorca, Spain E. Sala Á C. Balaguer Á A. Rı ´os Á B. G. Cosı ´o Á A. Noguera Á A. Agustı ´ Fundacio ´n Caubet-Cimera, International Center for Advanced Respiratory Medicine, Mallora, Balleares Islands, Spain E. Sala Á C. Villena Á C. Balaguer Á B. G. Cosı ´o Á A. Noguera Á A. Agustı ´ CIBER de Enfermedades Respiratorias (CIBERES), Biomedical Research Center Respiratory Disease Network, Bunyola, Mallora, Balleares Islands, Spain A. Agustı ´ Institut Clı ´nic del To `rax, Universitat de Barcelona, Barcelona, Spain 123 Lung (2010) 188:331–338 DOI 10.1007/s00408-009-9225-8